Lipoprotein lipase gene mutations in coronary artery disease

Genetic lipoprotein disorders are frequently associated with premature coronary artery disease (CAD). Functional mutations of the lipoprotein lipase (LPL) gene are associated with altered plasma lipoprotein profiles and are relatively common in French Canadians.

To investigate the prevalence of LPL gene mutations in a group of patients with premature CAD and in a healthy control group.

A total of 636 subjects (337 [82% men] with angiographically documented CAD and 299 controls [63% men]) were examined for the presence of mutations LPL(Gly188-->Glu), LPL(Pro207-->Leu), LPL(Asp250-->Asn) and LPL(Asn291-->Ser) of the LPL gene. These mutations represent over 97% of LPL mutations in familial hyperchylomicronemia in Quebec.

The prevalence of heterozygosity for defective LPL alleles was eight of 337 (2.4%) in the CAD group and five of 299 (1.7%) in the control group (chi(2) = 0.118, P = 0.73; power [P] for alpha = 0.05, P = 0.60). In the six CAD patients heterozygous for LPL(Asn291-->Ser), fasting plasma lipoprotein lipid levels did not differ significantly from those of the rest of the CAD group or markedly from those of control subjects. The two CAD patients heterozygous for the LPL(Gly188-->Glu) mutation, however, had hypertriglyceridemia and low plasma high density lipoprotein levels. No CAD or control subjects were identified with the LPL(Pro207-->Leu) or LPL(Asp250-->Asn) alleles.

In this selected population of premature CAD subjects, the prevalence of heterozygosity for defective LPL alleles was slightly higher (but not significantly so) than that in a group of healthy subjects. The LPL(Gly188-->Glu) and LPL(Asn291-->Ser) mutations may confer genetic susceptibility to premature CAD in a small number (approximately 2.4%) of patients; overall these four LPL alleles do not appear to contribute significantly to CAD risk in French Canadians.